Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR.10.

Abstract

PURPOSE:

High class III beta-tubulin (bTubIII) expression in advanced non-small cell lung cancer is known to correlate with reduced response rates and inferior survival with anti-microtubule agents. JBR.10 showed a 12% and 15% improvement in 5-year recurrence-free survival (RFS) and overall survival (OS), respectively, with the addition of cisplatin and vinorelbine following resection of stage IB-II non-small cell lung cancer. We sought to determine the effect of bTubIII on patient outcome and benefit from adjuvant chemotherapy in the JBR.10 trial.

EXPERIMENTAL DESIGN:

We did a semiquantitative immunohistochemical assay for bTubIII on primary tumor tissue available from 265 of the 482 patients in JBR.10. Tumors were classified as bTubIII "low" or "high" using a validated method. We examined the prognostic effect of bTubIII in patients treated with or without chemotherapy and the survival benefit from chemotherapy in low versus high bTubIII subgroups.

RESULTS:

High bTubIII expression was associated with poorer RFS and OS in patients treated with surgery alone but not in patients treated with adjuvant chemotherapy. The RFS and OS benefits of adjuvant chemotherapy were greater in high versus low tubulin expressors. However, with Cox regression, the interaction between bTubIII status and chemotherapy treatment in predicting RFS or OS did not reach statistical significance.

CONCLUSIONS:

Chemotherapy seemed to overcome the negative prognostic effect of high bTubIII expression. Greater benefit from adjuvant chemotherapy was seen in patients with high bTubIII expression. This is contrary to what has been seen in the setting of advanced disease; possible reasons for this difference are being explored.

• Authors: Pascal Sève, Raymond Lai, Keyue Ding, Timothy Winton, Charles Butts, John Mackey, Charles Dumontet, Laith Dabbagh, Sarit Aviel-Ronen, Lesley Seymour, Marlo Whitehead, Ming-Sound Tsao, Frances A Shepherd, Tony Reiman
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 3 Pg. 994-9 (Feb 01 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17289895 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• TUBB3 protein, human
• Tubulin
• Vinblastine
• Cisplatin
• Vinorelbine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Chemotherapy, Adjuvant
• Cisplatin (administration & dosage)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Prognosis
• Time Factors
• Treatment Outcome
• Tubulin (biosynthesis)
• Vinblastine (administration & dosage, analogs & derivatives)
• Vinorelbine